How a Study of a Failed Antidepressant Shows That Antidepressants Really Work

The British Medical Journal recently released a study finding that the antidepressant reboxetine, which is manufactured by Pfizer and has been used in Europe since 1997 — but is not approved in the U.S. — does not work at treating depression. The BMJ study looked at 13 clinical trials of reboxetine involving some 4,000 patients; Pfizer had never published data on 74% of those patients, which, as a result, inflated the drug’s apparent effectiveness over placebo by up to 115%. But hidden in this demoralizing research are two surprising pieces of good news.

The first is a reminder of a law passed in 2007 in the U.S., which requires drug companies to make public all data — positive and negative — from clinical trials on drugs regulated by the Food and Drug Administration (FDA). That law is protecting American consumers. Europe doesn’t have such a rule, which may be why reboxetine was approved there while the FDA failed to approve it in the U.S. So, props to Congress and the FDA on that one. (More on Time.com: SPECIAL — How Not to Get Sick).

The second positive implication of the reboxetine study involves the popular claim that no modern antidepressants work better than placebo. Supporters of this idea — most notoriously, psychologist Irving Kirsch — say that any mood-enhancing benefit of antidepressants can be attributed to the placebo effect, the phenomenon by which the mere expectation of getting better actually helps patients get better, even if the treatment they’re using is a sham.

Kirsch and others suggest that in the case of antidepressants, their beneficial effect is due entirely to the fact that they have side effects — these experiences provide cues to patients that the drugs must be working, which induces a placebo response. In trials, when antidepressants show actual benefit compared to placebo, detractors chalk it up to the fact that placebos that appear to really “do something” tend to produce stronger benefit than inactive sugar pills. (More on Time.com:Survey: 9% of Americans Are Depressed).

But if that were the case, then a drug like reboxetine, which indeed has numerous side effects, should have registered some kind of placebo effect. The anonymous neuroscientist “Neuroskeptic” said it well:

The existence of reboxetine, a drug which has lots of side effects, but doesn’t work, is evidence against the theory… [G]iven that reboxetine had more side effects than SSRIs, it ought to have worked better, but actually it worked worse. This is by no means the nail in the coffin of the active placebo hypothesis but it is, to my mind, quite convincing.

Moreover, the wide variance in individual responses to the class of antidepressants known as SSRIs tends to underplay the effectiveness of these drugs. That, combined with the fact that reboxetine did not perform better than placebo, suggests that the idea that depression drugs are just expensive sugar pills really misses the mark.